Association studies of ALOX5 and bone mineral density in healthy adults

Abstract

Animal studies suggest that arachidonate 5-lipoxygenase (encoded by ALOX5) may be a genetic determinant of bone mineral density. We tested this hypothesis in a sample of healthy men and women and did not find consistent evidence for an association between variation in this gene and either lumbar spine or femoral neck BMD. Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. A recent mouse study implicated ALOX5, which encodes arachidonate 5-lipoxygenase, as a contributing factor to areal BMD (aBMD). Fifteen single nucleotide polymorphisms (SNPs) distributed throughout ALOX5 were genotyped in three healthy groups: 1,688 European American, premenopausal sisters, 512 African American premenopausal sisters and 715 European American brothers. Statistical analyses were performed in the three groups to test for association between these SNPs and femoral neck and lumbar spine aBMD. Significant (p < or = 0.05) evidence of association was observed with three of the SNPs. However, despite the linkage disequilibrium between SNPs, adjacent SNPs did not provide statistical evidence of association in any of the three study groups. These data do not provide consistent evidence of association between genomic variation in ALOX5 and clinical variability in aBMD in healthy subjects.